The goal of the proposed research plan is to clarify the intrarenal neural pathways involved in autonomic control of renin secretion. It is known that renin secretion rate can be increased by neural stimulation of intrarenal beta-adrenoceptors. There is evidence that the renal nerves may also either stimulate or inhibit renin secretion by activation of intrarenal alpha-adrenoceptors. In addition, the kidney contains acetylcholinesterase-staining fibers; these may be parasympathetic postganglionic nerves. The ability of intrarenal alpha-adrenoceptors to mediate increased or decreased renin release will be studied in pentobarbital-anesthetized dogs by renal nerve stimulation and renal artery infusion of alpha-adrenergic agonists and tyramine, before and after intrarenal alpha-adrenergic blockade. Multiple agonist dosages and nerve stimulation levels, selected on the basis of their effects on renal vascular resistance, glomerular filtration rate and urinary sodium excretion, will be studied. The presence of a vagal innervation of the kidney will be tested neurophysiologically, and if confirmed, the effect of posterior vagal nerve stimulation on renin release will be studied. A possible role for renal cholinergic nerves in control of renin release will be evaluated by vagal or renal nerve stimulation, and by renal artery infusion of acetylcholine, before and after intrarenal muscarinic blockade. The renin-angiotensin system has an important role in maintaining cardiovascular homeostasis and has been implicated in the development of some forms of hypertension. These studies will expand our understanding of the neural control of renin secretion, and will aid in assessing the effects of pharmacological intervention with the autonomic nervous system in the treatment of cardiovascular disorders.